Cohort-based Analysis of Paternal Opioid Use in Relation to Offspring's BMI and Plasma Lipid Profile

A growing body of evidence suggests that opioid use may affect consumer's offspring by second-hand passive smoke exposure, as well as by transgenerational impacts mediated by genetic and epigenetic alterations of paternal gametes. In human studies, these effects are limited to investigating the neural, behavioral and cognitive characteristics of offspring. Only animal studies have investigated the metabolic parameters influenced by passive opium smoke exposure. Here, we conducted population-based analyses aimed to estimate the association of paternal opioid consumption, started before or after child birth, with BMI status and plasma lipid profile of young adult offspring. The present study includes 840 parents-offspring trios (offspring aged 15-35, parents aged 35-70) who participated in the prospective Rafsanjan Cohort Study (RCS)-a city in the south-east of Iran-as one of the district areas of the PERSIAN cohort (Prospective Epidemiological Research Studies in IrAN). All procedures for interviews, anthropometric measurements and physical examinations, biological sample collection and laboratory tests for blood biochemical parameters were conducted according to the PERSIAN cohort protocol, and in the well-established RCS setting. Crude and adjusted multiple logistic regression analysis were conducted to assess the relationship of paternal regular opioid use with offspring's BMI status, and plasma lipid factors. The prevalence of fathers who use opioids regularly among the studied trios was 42.8% (360/840). Our regression analyses demonstrated that paternal opioid use started pre-fatherhood is associated with 76% higher adjusted odds ratio (OR) of overweight/obesity in young offspring (adjusted OR 1.76 (95% CI 1.15-2.71)), adjusting for sex, age, parental BMIs, paternal smoking status and socioeconomic status index (WSI). This relationship persisted when fathers who used opioid by routes other than inhaling (oral) were excluded from logistic analysis (adjusted OR 1.73 (95% CI 1.12-2.68)). Interestingly, sex stratified analysis displayed a 201% increased odds ratio of overweight/obesity in sons of fathers who use opioid regularly, started after child birth (Adjusted OR 3.01 (95% CI 1.68-5.39), while no significant association was found in daughters (adjusted OR 0.74 (95% CI 0.35-1.54)). Additionally, increasing exposure-response relationships were observed between odds ratios of overweight/obesity and the number of years of paternal opioid use after birth (p-trend = 0.0008). Paternal regular opioid use started pre-fatherhood was associated with 54% lowered risk of underweight [adjusted OR 0.46 (95% CI 0.24-0.86)]. Finally, paternal opioid consumption started either before or after child birth did not show a significant association with the high level of the three parameters of plasma lipid factors (triglyceride, cholesterol and HDL-cholesterol) in offspring. Our results suggest that the environmental impacts of paternal regular opioid use may be sufficient to make an effect on male offspring metabolism independent of genetic and epigenetic impact on gametes.